1/30. Caesarean section in a patient with paramyotonia congenita. This case report details spinal anaesthesia for an elective caesarean section in a patient with the rare condition of paramyotonia congenita. There are few case reports of anaesthesia in this condition and none in the Australian anaesthetic literature. This case highlights the need for the avoidance of hypothermia and depolarizing muscle relaxants, the safety of spinal anaesthesia and a conservative approach to the management of plasma potassium concentration. The subsequent review outlines the current literature and discusses other issues involved in the anaesthetic management of this disorder. ( info) |
2/30. Proximal myotonic myopathy: clinical, electrophysiological and pathological findings in a family. Proximal myotonic myopathy (PROMM) is an autosomal dominant muscle disorder characterized by proximal weakness, myotonia, muscle pain and cataract. It resembles Steinert myotonic dystrophy (MD), but weakness is proximal, without facial muscle involvement, and the chromosome 19 CTG trinucleotide repeat expansion characteristic of MD is not present. We describe a further family with PROMM. Affected members complained of weakness of lower limbs or of myotonia. EMG revealed diffuse myotonic discharges. Muscle histology showed dystrophic abnormalities. The PROMM phenotype varies, even in the same pedigree, and may mimic MD or limb-girdle muscle dystrophy. EMG is particularly useful, since it may disclose myotonic discharges even in the absence of overt myotonia. Thus far it is not known whether PROMM is a single entity, or if it represents a heterogeneous group of disorders. This question will probably soon be settled through genetic analysis. ( info) |
3/30. Proximal myotonic myopathy: clinical and molecular investigation of a Norwegian family with PROMM. Proximal myotonic myopathy (PROMM) was first described in 1994 as a multisystem disorder with similarity to myotonic dystrophy (DM), but without the abnormal (CTG)n expansion in the DM protein kinase (DMPK) gene. The inheritance is autosomal dominant and the clinical features include myotonia, proximal muscle weakness and cataract. Linkage analysis in nine German PROMM families has indicated the possibility of linkage to DM2 locus on chromosome 3. We report a Norwegian PROMM family in which the proband was clinically diagnosed as DM but without the (CTG)n expansion. Using an intragenic marker we showed that the DMPK gene did not segregate with the disease in this family. All family members are heterozygous for the R894X mutation in CLCN1 gene. Linkage analysis could not be performed, but haplotyping probably excludes the DM2 locus as the disease locus in this family. The present family emphasises that myalgia is a prominent symptom in PROMM and the clinical differences may be explained by genetic heterogeneity. This family will be reinvestigated along with the identification of candidate genes or regions in larger PROMM families. ( info) |
4/30. X-linked myotubular myopathy--a long-term follow-up study. X-Linked myotubular myopathy is a well delineated congenital myopathy, with a high neonatal and early childhood mortality. Only a single gene, mapping to Xq28 has been implicated and has recently been characterized. Phenotypic variability, both inter- and intrafamilial, has been recorded. Its severest expression is a uniform disease with polyhydramnios due to prenatal (neuromuscular) swallowing disorder, and partial inability to expand the lungs postnatally leading to early postnatal death in all. The mildest expression appears to be represented by the first family reported in the literature in which intrafamilial phenotypic variability was marked. There was neonatal asphyxia, but recovery took place in most affected patients and very mild expression permitting normal life into adulthood has been found in two patients. A long-term follow-up is given on both these families. Results emphasize the importance of the family history when trying to prognosticate in an individual case. ( info) |
5/30. Clinical, electrophysiological, and molecular genetic studies in a new family with paramyotonia congenita. OBJECTIVES: To characterise the clinical and electrophysiological features and to determine the molecular genetic basis of pure paramyotonia congenita in a previously unreported large Irish kindred. methods: Clinical and neurophysiological examination was performed on three of the five affected family members. Five unaffected and three affected members of the family were available for genetic testing. Direct sequence analysis of the SCN4A gene on chromosome 17q, was performed on the proband's dna. Restriction fragment length polymorphism (RFLP) analysis was used to screen other family members and control chromosomes for the SCN4A mutation identified. RESULTS: Each affected member had clinical and examination features consistent with pure paramyotonia congenita. Electrophysiological studies disclosed a 78% drop in compound muscle action potential (CMAP) amplitude on cooling to 20 degrees C. dna sequence analysis identified a heterozygous point mutation G4367A in exon 24 of the SCN4A gene which segregated with paramyotonia and was absent in 200 control chromosomes. The mutation is predicted to result in a radical amino acid substitution at a highly conserved position within the voltage sensing fourth transmembrane segment of the fourth repeated domain of the sodium channel. CONCLUSIONS: The G4367A mutation is likely to be pathogenic and it associates with a pure paramyotonia phenotype. In keeping with other paramyotonia mutations in this region of the skeletal muscle sodium channel, it is predicted that this mutation will impair voltage sensing or sodium channel fast inactivation in a temperature dependent fashion. This study provides further evidence that exon 24 in SCN4A is a hot spot for paramyotonia mutations and this has implications for a dna based diagnostic service. ( info) |
6/30. hypothyroidism unmasking proximal myotonic myopathy. No specific diagnostic test is available to identify patients with proximal myotonic myopathy and to distinguish them from common disorders causing similar complaints. We describe three patients from three separate families who were initially diagnosed as having hypothyroid myopathy. Proximal weakness, stiffness and myotonia have persisted in each patient (2-10 years) despite the restoration of the euthyroid state. A familial pattern of autosomal dominant inheritance for proximal weakness, myotonia, and cataracts was clearly identified in one family and was likely in the other two families. dna testing showed normal size of CTG repeat in the gene for myotonic dystrophy. The clinical presentation of these three patients strongly suggests that hypothyroidism can unmask PROMM in asymptomatic individuals who carry the genetic abnormality. Other cases of 'hypothyroid myopathy' may represent examples of unmasked PROMM. ( info) |
7/30. hyperparathyroidism in a patient with proximal myotonic myopathy (PROMM). We describe a 60-year-old woman with progressive proximal leg weakness and dystrophic changes of the quadriceps and the adductor muscles on magnetic resonance imaging. She also suffered from primary hyperparathyroidism. A biopsy of the left deltoid muscle showed vacuoles as an unusual histopathological finding. ( info) |
8/30. Spectrum of Schwartz-Jampel syndrome includes micromelic chondrodysplasia, kyphomelic dysplasia, and Burton disease. Follow-up and re-evaluation of four patients originally described as examples of severe infantile "micromelic chondrodysplasia" resembling Kniest disease, "kyphomelic dysplasia," and "Burton skeletal dysplasia" revealed the diagnosis of Schwartz-Jampel syndrome (SJS, myotonic chondrodysplasia) in all of them. SJS may be suspected in neonates with Kniest-like chondrodysplasia, congenital bowing of shortened femora and tibiae, and facial manifestations consisting of a small mouth, micrognathia, and possibly pursed lips. The disorder must be differentiated from the Stuve-Wiedemann syndrome, a genetically distinct myotonic chondrodysplasia with similar clinical but different skeletal changes and an unfavorable early prognosis. The demise of "kyphomelic dysplasia" as a nosological entity reemphasizes the symptomatic nature of congenital bowing of the long bones. ( info) |
9/30. Proximal myotonic myopathy: clinical, neuropathologic, and molecular genetic features. The primary genetic abnormality in myotonic dystrophy (DM) is an expansion of the CTG trinucleotide repeat on chromosome 19q. Recently, patients with similar clinical features, but without this genetic alteration, have been designated as proximal myotonic myopathy (PROMM). We describe two additional cases of PROMM, both of whom presented with clinical features suggestive of myotonic dystrophy. The patients had electromyographic (EMG) evidence of myotonia, normal cardiac evaluation, and no cataracts. Genetic analysis of peripheral blood leukocytes revealed no expansion of the trinucleotide repeat by polymerase chain reaction (PCR) and Southern blot analysis. Muscle biopsies in both cases were significant with features suggestive of myotonic dystrophy, such as large numbers of fibers containing multiple internal nuclei, occasional nuclear chains, and fiber atrophy, although sarcoplasmic masses and ring fibers were absent. These cases illustrate the clinical and neuropathologic findings of PROMM and underline the importance of correlating these aspects with genetic studies in patients with myotonic muscle disorders. ( info) |
10/30. Proximal myotonic myopathy and proximal myotonic dystrophy: two different entities? The phenotypic variability of proximal myotonic syndromes. Multisystemic myotonic myopathies are characterised by a variable pattern of symptoms and signs and a variable degree of disease severity. Proximal myotonic dystrophy has been described as an entity distinct from proximal myotonic myopathy because of severe proximal muscle weakness and dystrophic changes on magnetic reasonace imaging and on muscle histopathology. We describe two siblings, one of them presenting with a proximal myotonic myopathy phenotype, the other with a proximal myotonic dystrophy-like phenotype. The variability of disease expression in these two siblings suggests that a proximal myotonic dystrophy-like variant may occur in proximal myotonic myopathy. ( info) |